Wednesday, December 4, 2024 12/4/2024

Pathophysiologic and Therapeutic Mechanisms of Aspirin Exacerbated Respiratory Disease

Award Number: U19AI095219
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Abstract

Overall Summary/Abstract This Asthma and Allergic Disease Cooperative Research Center (AADCRC) continues its focus on the mechanistic basis of respiratory tract type 2 immunopathology (T2I), particularly in aspirin-exacerbated respiratory disease (AERD), a distinctive clinical syndrome that accounts for a disproportionate percentage of individuals with severe asthma and recurrent chronic rhinosinusitis with nasal polyposis (CRSwNP). In the current period of support, we discovered marked epigenetically imprinted abnormailites in epithelial basal cell (BC) function and differentiation underlying CRSwNP and AERD, some of which are driven by strong, persistent signaling through the interleukin 4 receptor alpha (IL-4Rα) and some by altered Wnt/Notch signaling. We identified dramatic hyperplasia of mast cells (MCs) in CRSwNP tissue, especially from individuals with AERD, driven in part by a novel, transcriptionally and cytofluorographically distinct MC population with a high rate of proliferation. We now have strong evidence that MC-stromal interactions drive many pathophysiologic features of respiratory T2I, and that these interactions are regulated by synergistic inputs from IL-4Rα and IL- 33/ST2 signaling axes. A tightly interactive team of accomplished investigators with complementary skills will apply cellular, molecular, and whole animal strategies, combined with a proof-of-concept clincal trial to determine the mechanistic basis for these findings, their relevance to disease pathophysiology, and their amenability to therapy. Project 1 (J. Boyce, PI) focuses on the the developmental origins of respiratory tract MCs, how their interactions with stromal cells dictate MC development and function and are altered by IL-4Rα signaling, and how MCs drive altered stromal cell function through a feed-forward loop involving IL-6 and leukemia inhibitory factor. Project 2 (N. Barrett, PI) focuses on the mechanisms by which epigenetic reprogramming of BCs combines with IL-4Rα signaling to drive BC dysplasia and sensecence as a disease- causing mechanism. Project 3 (T. Laidlaw, PI) will compare the efficacy of IL-4Rα blockade with IL-33 blockade in a proof of mechanism placebo controlled trial, focusing on restoration of BC function and suppression of MC hyperplasia and activation. The Projects are supported by respective Cores for Adminstration (Core A), and Integrative Genomics (Core B).


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	14	11/20/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $1,699,971 )
2024	2024	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	14	4/5/2024	NON-COMPETING CONTINUATION	$1,535,611
2024	2024	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	13	12/18/2023	SUPPLEMENT FOR EXPANSION	$173,820
2024	2020	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	10	10/13/2023	SUPPLEMENT FOR EXPANSION	-$9,460
														Subtotal = $1,699,971

Issue Date FY: 2023 ( Subtotal = $1,535,611 )
2023	2023	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	13	5/12/2023	NON-COMPETING CONTINUATION	$1,535,611
														Subtotal = $1,535,611

Issue Date FY: 2022 ( Subtotal = $1,535,611 )
2022	2022	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	003	12	5/24/2022	NON-COMPETING CONTINUATION	$1,535,611
2022	2021	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	11	4/6/2022	COMPETING CONTINUATION	$576,463
2022	2020	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	10	4/6/2022	NON-COMPETING CONTINUATION	-$576,463
2022	2020	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	10	4/7/2022	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $1,535,611

Issue Date FY: 2021 ( Subtotal = $1,535,096 )
2021	2021	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	11	7/23/2021	COMPETING CONTINUATION	$1,535,096
2021	2020	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	10	7/15/2021	NON-COMPETING CONTINUATION	$0
2021	2020	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	10	5/4/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,535,096

Issue Date FY: 2020 ( Subtotal = $1,657,559 )
2020	2020	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	10	7/24/2020	SUPPLEMENT FOR EXPANSION	$114,202
2020	2020	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	10	6/9/2020	NON-COMPETING CONTINUATION	$1,543,357
														Subtotal = $1,657,559

Issue Date FY: 2019 ( Subtotal = $1,543,357 )
2019	2019	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	003	9	7/5/2019	NON-COMPETING CONTINUATION	$1,543,357
2019	2016	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	6	2/9/2019	COMPETING CONTINUATION	-$12,500
2019	2015	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	5	2/9/2019	NON-COMPETING CONTINUATION	$12,500
2019	2015	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	5	2/12/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,543,357

Issue Date FY: 2018 ( Subtotal = $1,978,951 )
2018	2018	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	8	5/25/2018	NON-COMPETING CONTINUATION	$1,543,357
2018	2017	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	7	11/24/2017	NON-COMPETING CONTINUATION	$435,594
														Subtotal = $1,978,951

Issue Date FY: 2017 ( Subtotal = $1,543,357 )
2017	2017	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	7	6/28/2017	NON-COMPETING CONTINUATION	$1,543,357
2017	2016	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	6	2/8/2017	COMPETING CONTINUATION	$453,719
2017	2015	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	5	2/8/2017	NON-COMPETING CONTINUATION	-$453,719
														Subtotal = $1,543,357

Issue Date FY: 2016 ( Subtotal = $1,543,357 )
2016	2016	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	6	6/13/2016	COMPETING CONTINUATION	$1,543,357
														Subtotal = $1,543,357

Issue Date FY: 2015 ( Subtotal = $1,986,118 )
2015	2015	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	5	6/29/2015	NON-COMPETING CONTINUATION	$1,816,003
2015	2015	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	5	8/25/2015	NON-COMPETING CONTINUATION	$170,115
2015	2015	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	5	8/12/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,986,118

Issue Date FY: 2014 ( Subtotal = $2,410,594 )
2014	2014	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	003	4	8/22/2014	SUPPLEMENT FOR EXPANSION	$148,056
2014	2014	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	004	4	8/22/2014	NON-COMPETING CONTINUATION	$147,979
2014	2014	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	4	6/20/2014	NON-COMPETING CONTINUATION	$1,787,094
2014	2014	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	4	8/13/2014	NON-COMPETING CONTINUATION	$0
2014	2013	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	3	6/9/2014	NON-COMPETING CONTINUATION	$327,465
														Subtotal = $2,410,594

Issue Date FY: 2013 ( Subtotal = $1,952,502 )
2013	2013	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	3	8/19/2013	NON-COMPETING CONTINUATION	$272,631
2013	2013	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	3	8/20/2013	NON-COMPETING CONTINUATION	$0
2013	2013	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	3	7/24/2013	NON-COMPETING CONTINUATION	$1,679,871
														Subtotal = $1,952,502

Issue Date FY: 2012 ( Subtotal = $1,787,094 )
2012	2012	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	7/2/2012	NON-COMPETING CONTINUATION	$1,787,094
														Subtotal = $1,787,094

Grand Total All Awards = $24,492,075

Page 1 of 2 (53 items)12

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Pathophysiologic and Therapeutic Mechanisms of Aspirin Exacerbated Respiratory Disease

Award Number: U19AI095219

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer